DESCRIPTION (Applicant's Description) The AIDS epidemic was recognized in part because of the occurrence of unusual malignancies in gay men. Despite empiric advances in the treatment of AIDS malignancies, only a minority of affected patients are cured of their malignancies. The presence of HHV-8 in Kaposi's sarcoma, Epstein-Barr virus (EBV) in a large subset of AIDS-associated lymphomas, and both viruses in primary effusion lymphomas (PELs) provides an important handle for the investigation of the pathogenesis and ultimately the specific treatment of these neoplasms. The overall goal of this Program Project is to investigate herpesvirus genes relevant to tumorigenesis, prevention, and treatment. Project 1 (Gary S. Hayward) will focus on the candidate HHV-8 transporting genes ORK1 and ORF-K15. Project 2 (Paula Pitha-Rowe) will focus on HHV-8 genes homologous to the cellular proteins of interferon response factors (IRF). Project 3 (John Nicholas) will focus on the HHV-8 homologue of interleukin-6 (IL-6) which may play a role in supporting neoplastic proliferation. Project 4 (S. Diane Hayward) will focus on interactions between HHV-8 and EBV. Project 5 (Richard F. Ambinder) will focus on pharmacologic induction of HHV-8 and EBV encoded enzymes as a strategy to selectively kill virus infected tumor cells. The overall objective of this program project grant is to define the clinical role of radiolabeled, genetically engineered antibodies directed against anti- carcinoembryonic antigen (CEA).